Synthesis and anti-SARS-CoV-2 activity and mechanism research of lycorine derivatives / 药学学报

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC50) and selectivity index (SI) values of 2.36 μmol·L-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (KD) value of 1.36 μmol·L-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Biosensor analysis technology and its research progress in drug development of Alzheimer's disease / 药学学报

Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.

Effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome based on 16S rDNA technique / 中国针灸

OBJECTIVES@#To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique.@*METHODS@#Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected.@*RESULTS@#After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group.@*CONCLUSIONS@#Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.

Application and development of quantitative nuclear magnetic resonance technology / 药学学报

Quantitative nuclear magnetic resonance (qNMR) technology has significant advantages in quantification due to its simple sample processing and high reproducibility. Two-dimensional qNMR analysis, which can solve the quantification problem of different components in complex systems, has gradually been applied in medicine, food, metabonomics, chemical engineering, and other fields. This paper reviews the analysis methods, influencing factors, experimental optimization, application fields, and other aspects of qNMR to promote its wide and effective application.

Recent advances in chemical fluorescent probes sensitive to tumor microenvironments / 药学学报

Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Advances in liquid-phase microextraction technology and its application in biological sample pretreatment / 药学学报

Liquid-phase microextraction is a novel pretreatment technique for biological samples developed on the basis of liquid-phase extraction technology, which is simple, rapid, economical, and environmentally friendly, and has been widely used in the analysis of biological matrix samples such as blood, urine, and saliva. In this paper, we review the basic principles of the main modes of liquid-phase microextraction techniques, i.e., single-drop microextraction, dispersive liquid-liquid microextraction, and hollow-fiber liquid-phase microextraction, and the progress of their applications in biological sample pretreatment by reviewing the literature in the past five years, with a view to providing technical support and reference for sample pretreatment in the fields of in vivo drug analysis, pharmacokinetic studies and new drug development.

Generation of male germ cells in vitro from the stem cells / 亚洲男科学杂志(英文版)

Infertility has become a serious disease since it affects 10%-15% of couples worldwide, and male infertility contributes to about 50% of the cases. Notably, a significant decrease occurs in the newborn population by 7.82 million in 2020 compared to 2016 in China. As such, it is essential to explore the effective methods of obtaining functional male gametes for restoring male fertility. Stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), spermatogonial stem cells (SSCs), and mesenchymal stem cells (MSCs), possess the abilities of both self-renewal and differentiation into germ cells. Significantly, much progress has recently been achieved in the generation of male germ cells in vitro from various kinds of stem cells under the specified conditions, e.g., the coculturing with Sertoli cells, three-dimensional culture system, the addition of growth factors and cytokines, and/or the overexpression of germ cell-related genes. In this review, we address the current advance in the derivation of male germ cells in vitro from stem cells based on the studies of the peers and us, and we highlight the perspectives and potential application of stem cell-derived male gametes in reproductive medicine.

A nomogram for preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma based on inflammation-related markers / 中华外科杂志

Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.

Detection of SMO gene mutations in odontogenic keratocyst / 中华口腔医学杂志

Objective: To detect the SMO mutations in odontogenic keratocyst (OKC) and to explore the mechanism behind. Methods: Patients with OKC who received treatment in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology,Peking University, from September 2012 to June 2017 were enrolled. OKC samples from 10 patients diagnosed as naevoid basal cell carcinoma syndrome (NBCCS)-related OKC (4 females and 6 males) and 20 patients diagnosed as sporadic OKC (7 females and 13 males) were collected. Genomic DNAs were extracted from fibrous capsules and epithelial lining respectively. SMO mutations were detected and analyzed by Sanger sequencing. Results: Three SMO mutations were found in one NBCCS-associated OKC who carrying c.2081C>G (p.P694R) mutation) and two sporadic OKC who carrying c.907C>T (p.L303F) mutation and c.1247_1248delinsAA (p.G416E), respectively), among which the first two mutations were novel mutations that had not been reported before. Besides, two mutations in sporadic OKC were not paired with PTCH1 mutations. Conclusions: In addition to PTCH1 gene mutations, SMO gene mutations also exist in OKC which might be related to the development of OKC.

Assessment of retinal microcirculation alterations in glaucoma by optical coherence tomography angiography / 中华实验眼科杂志

Microcirculation alterations of the human retina are of significant relevance with glaucoma.Optical coherence tomography angiography (OCTA) is a non-invasive examination that provides signals of the retina and retinal microcirculation.It is currently widely used in research and screening for glaucoma due to its effective detection of each layer in the retinal microcirculation.Vessel density of radial peripapillary capillary (RPC) is positively correlated with the retinal nerve fiber layer thickness, which is crucial in the assessment of glaucoma.Peripapillary region and macula are regions of interest in OCTA analysis for microcirculation.Vessel density of the whole retina and RPC in the peripapillary region decreases significantly, which matches the thinned retinal fiber layer thickness and visual field defects, and is relevant to the disease severity.As for the macular region, vessel density declines while the area of the foveal avascular zone increases.Greater changes in late-stage glaucoma and normal-tension glaucoma are detected by OCTA compared with other stages and types of glaucoma.OCTA imaging may be influenced by high myopia and intraocular pressure, and the peripapillary region is of greater diagnostic value than macula in microcirculation changes.In conclusion, OCTA can serve as a new technique for the assessment of retinal microcirculation in glaucoma.This review summarized the characteristics of retinal microcirculation in OCTA images and its change in peripapillary and macular region in glaucoma eyes.Influencing factors associated with peripapillary and macular microcirculation changes in OCTA images and evaluation of peripapillary and macular microcirculation in glaucoma by OCTA and their diagnostic values were reviewed.

Effects of bisphenols on proliferation and oxidative stress of BRL 3A rat liver cells and their mutagenicities / 预防医学

Objective@#To examine the effects of bisphenol A (BPA), bisphenol S ( BPS ), bisphenol F ( BPF ) and bisphenol AF ( BPAF ) on the proliferation and oxidative stress of BRL 3A rat liver cells, and to preliminarily evaluate their mutagenicities.@*Methods@#In vitro cultured BRL 3A rat liver cells were treated with BPA, BPS, BPF and BPAF at concentrations of 0, 5, 10, 25, 50, 100, 150 and 200 μmol/L for 48 h, respectively. Then, the cell viability was determined using the CCK-8 assay, and the half maximal inhibitory concentration ( IC50 ) was calculated. The minimum inhibitory concentration for BRL 3A cell proliferation was screened, and the intracellular reactive oxygen species ( ROS ) was measured in BRL 3A cells using the 2',7'-dichlorodihydrofluorescein diacetate ( DCFH-DA ) assay. In addition, the effects of BPA, BPS, BPF and BPAF at concentrations of 1 000, 200, 40, 8 and 1.6 μg/plate on the mutant colonies of histidine-deficient Salmonella typhimurium ( TA1535, TA97a, TA98, TA100 and TA102 ) were tested using the Ames test.@*Results@#Treatment with BPA and BPF at concentrations of 100 to 200 μmol/L and with BPAF at concentrations of 25 to 200 μmol/L inhibited BRL 3A cell survival at a concentration-dependent manner, while exposure to BPS at concentrations of 5 to 200 μmol/L resulted in no changes in BRL 3A cell survival. The IC50 values of BPA, BPS, BPF and BPAF were 131.7, >200, 187.5 and 21.6 μmol/L against BRL 3A cells, respectively. Treatment with BPS at 100 μmol/L or BPAF at 25 μmol/L caused no significant changes in the ROS level; however, exposure to BPA at 100 μmol/L and BPF at 100 μmol/L significantly increased the ROS level. Ames test showed that BPA, BPS, BPF and BPAF did not induce mutagenicity in TA1535, TA97a, TA98, TA100 or TA102 strains.@*Conclusions@#BPAF shows the highest cytotoxicity to BRL 3A cells, and low-concentration exposure to BPS has few effects on BRL 3A cells. The cytotoxicity of bisphenols against BRL 3A cells may be associated with the induction of oxidative stress. None of the four bisphenols show mutagenic effects under the present experimental conditions.

A proposed mechanism by which Qishen Yiqi dropping pill improves cardiac energy metabolism in rats with heart failure based on metabolomics and network pharmacology / 药学学报

"Omics" and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.

Construction of a blood-brain barrier microfluidic chip model and evaluation of the permeability of active components in traditional Chinese medicine / 药学学报

A blood-brain barrier microfluidic chip platform for studying the permeability of active components in traditional Chinese medicine was developed. This model used primary human brain microvascular endothelial cells on a microfluidic chip consisting of two perpendicularly-crossing channels and a single layer porous polycarbonate membrane. The physiological shear stress in the human vasculature was also modeled in this device. Cell viability on the chip was monitored by cell staining and immunofluorescence staining. The cells spread well and the structure of an intercellular adhesion protein was satisfactory. The permeability of fluorescent tracers and three model drugs and the functional expression of P-glycoprotein (P-gp)on the blood-brain barrier were investigated. The results show that the apparent permeability coefficients (Papp) of the fluorescent tracers and three model drugs were consistent with those reported in the literature, and P-gp on the chip showed normal function, indicating that there was a complete structure and a functional BBB. The permeability of six active components of traditional Chinese medicine was investigated through this microfluidic chip and the drug concentration was determined by HPLC-MS/MS to obtain the Papp of each component. The Papp of corydaline was (4.51 ± 1.90)×10-7 cm·s-1, the Papp of tetrahydropalmatine was (9.10 ± 6.59)×10-7 cm·s-1, and the Papp of imperatorin was (9.38 ± 2.53)×10-7 cm·s-1; the concentration of isoimperatorin, baicalin and chlorogenic acid was below the limit of quantification, which suggested that isoimperatorin, baicalin and chlorogenic acid have poor permeability in this BBB chip. This blood-brain barrier microfluidic platform possesses a complete barrier function and near-physiological conditions and could be a valuable in vitro tool for drug permeability evaluation.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction / 中国药理学与毒理学杂志

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. METHODS The patients with coronary heart dis?ease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months, and the changes of cardiac function were observed. 61 serum samples (including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group) were analyzed by non labeled proteomics. The disease group was used as the control group, and the protein with expression level difference of more than 1.2 folds (P<0.05) was screened. The molecular function, biologi?cal pathway and protein interaction of the different proteins were analyzed by bioinformatics, so as to identify the molecu?lar and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction, regulate blood glucose and blood lipid levels, prolong thrombin time, and improve heart function. The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group. Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1, alpha-2 and other proteins to act on HDL assembly, platelet degradation, PI3K Akt signaling pathway, and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome. CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syn?drome of coronary heart disease. It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins. This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Desulfovibrio vulgaris, a potent acetic acid-producing bacterium, increased by Astragalus polysaccharides to attenuate nonalcoholic fatty liver disease in mice / 中国药理学与毒理学杂志

OBJECTIVE Although the underlying mechanism is largely unknown, gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease (NAFLD), type 2 diabetes and meta?bolic syndrome. The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome. So, our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides (APS) extracted from Astragalus mongholicus Bunge in high-fat diet (HFD) fed mice. METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS. Then, targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids (SCFAs) and bacteria that were specifically enriched by APS. Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium. Finally, the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice. RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota. Moreover, our results indicated that SCFAs, predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment. Metagenomics revealed that D. vulgaris from Desulfovibrio genus was not only enriched by APS, but also a potent generator of acetic acid, which showed significant anti-NAFLD effects in HFD fed mice. In addition, D. vulgaris modulated the hepatic gene expression pattern of lipids metabolism, particularly suppressed hepatic fatty acid synthase (FASN) and CD36 protein expression. CONCLUSION APS enriched D. vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid, and modulation on hepatic lipids metabolism in mice. Further studies are warranted to explore the long-term impacts of D. vulgaris on host metabolism and the underly?ing mechanism.

Research progress on the role of non-image forming functions of eyes in magnetoreception of organisms / 中华实验眼科杂志

Non-image forming functions of eyes include the regulation of biological circadian rhythm and biological magnetoreception.Biological magnetoreception means that various organisms including human obtain the direction and position information through the geomagnetic field.Creatures with retina realize magnetoreception regarding retinal cryptochrome as magnetoreceptor.Hypotheses of magnetoreception contain the radical-pair theory and the biological compass theory.The two theories both reckon retinal elements as possible receptor protein of magnetoreception, and eyes as receptor organ.The radical-pair theory suggests that change of radical spin influences the structure of retinal cryptochrome, leading to different downstream chemical reaction products, which makes the variable magnetic field information perceivable.And the biological compass theory proposes a rod-like complex composed of polymerized cryptochromes and magnetoreceptor proteins, which can point to different directions due to light and magnetic signals.These changes in retina transmit geomagnetic field signal to the brain, and then sense of direction is formed.Researching biological magnetoreception promotes a novel perspective in the diagnosis and treatment of eye and brain diseases, and brings innovation in magnetic material field.In this article, non-image forming functions of eyes, hypotheses of magnetoreception and possible mechanism of non-image forming functions of eyes in magnetoreception were reviewed.

Analysis of Chemical Constituents in Daishenning by HPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective:High performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （HPLC-Q-TOF-MS/MS） was used to identify the main chemical constituents of Daishenning. Method:Cosmosil 5 C₁₈-AR-Ⅱ column （4.6 mm×250 mm， 5 μm） was employed for chromatographic separation with mobile phase of acetonitrile （A）-0.5% formic acid aqueous solution （B） for gradient elution （0-10 min， 5%A； 10-20 min， 5%-20%A； 20-30 min， 20%A； 30-55 min， 20%-35%A； 55-65 min， 35%-55%A； 65-75 min， 55%-100%A； 75-80 min， 100%A； 80-85 min， 100%-5%A； 85-90 min， 5%A）， the flow rate was 1 mL·min^-1， column temperature was 40 ℃， and injection volume was 10 μL. Electrospray ionization （ESI）， positive and negative ion detection modes and mass scanning range of <italic>m</italic>/<italic>z</italic> 100-2 000 were selected for mass spectrometry. The main chemical constituents in Daishenning were identified by MassHunter B.06.00 software in combination with PubChem， MassBank， ChemicalBook and other databases， and reference information. Result:A total of 96 components were identified from Daishenning， including 32 flavonoids， 19 organic acids， 6 glycosides， 6 terpenoids， 5 phenylpropanoids， 8 phenols， 14 other components and 6 unknown components. Conclusion:The established method can simultaneously analyze different types of compounds in Daishenning， it is helpful for further research on the extraction and separation of main chemical components and quality control of this preparation. In addition， through the rapid identification of the chemical constituents in Daishenning， it is speculated that the main effective substances of Daishenning may be flavonoids and organic acids.

Platelet antibody screening and crossmatch in Chengdu in 2019 / 中国输血杂志

【Objective】 To analyze the status of the platelet antibody screening and crossmatch in Chengdu in 2019, so as to further improve the corresponding detection strategy to improve the clinical transfusion efficacy. 【Methods】 The patients underwent platelet antibody crossmatch in Chengdu Blood Center in 2019 were selected as research objects Platelet antibody screening and crossmatch were performed by solid-phase agglutination technique, and the sample size, the incidence of platelet antibod, age, blood group, seasonal chracteristics, hospital levels, ratio of repeated crossmatch and the transfusion efficacy were analyzed. 【Results】 321 treatment doses of matched platelets after 259 occasions of crossmatch relative to 85 patients were provided. The positive rate of platelet antibody was 87.06%. 64.71% of the patients were over 40 years old, the proportion of ABO group in crossmatch samples was O>A>B>AB, and the crossmatch cases increased each quarter gradually. All samples were provided by tertiary hospitals. 52.94% of the patients needed crossmatch at least twice, and the efficacy rate of matched platelets transfusion was 63.64%. 【Conclusion】 The platelet transfusion efficacy could by improved by platelet antibody screening and crossmatch, so as to avoid the waste of platelets, which deserves active promotion in clinical.